Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Louise V. Wain, Germaine C. Verwoert, Paul F. O'Reilly, Gang Shi, Toby Johnson, Andrew D. Johnson, Murielle Bochud, Kenneth M. Rice, Peter Henneman, Albert V. Smith, Georg B. Ehret, Najaf Amin, Martin G. Larson, Vincent Mooser, David Hadley, Marcus Dörr, Joshua C. Bis, Thor Aspelund, Tõnu Esko, A. Cecile J W JanssensJing Hua Zhao, Simon Heath, Maris Laan, Jingyuan Fu, Giorgio Pistis, Jian'An Luan, Pankaj Arora, Gavin Lucas, Nicola Pirastu, Irene Pichler, Anne U. Jackson, Rebecca J. Webster, Feng Zhang, John F. Peden, Helena Schmidt, Toshiko Tanaka, Harry Campbell, Wilmar Igl, Yuri Milaneschi, Jouke Jan Hottenga, Veronique Vitart, Daniel I. Chasman, Stella Trompet, Jennifer L. Bragg-Gresham, Behrooz Z. Alizadeh, John C. Chambers, Xiuqing Guo, Terho Lehtimäki, Brigitte Kühnel, Lorna M. Lopez, Ozren Polašek, Mladen Boban, Christopher P. Nelson, Alanna C. Morrison, Vasyl Pihur, Santhi K. Ganesh, Albert Hofman, Suman Kundu, Francesco U S Mattace-Raso, Fernando Rivadeneira, Eric J G Sijbrands, Andre G. Uitterlinden, Shih Jen Hwang, Ramachandran S. Vasan, Thomas J. Wang, Sven Bergmann, Peter Vollenweider, Gérard Waeber, Jaana Laitinen, Anneli Pouta, Paavo Zitting, Wendy L. McArdle, Heyo K. Kroemer, Uwe Völker, Henry Völzke, Nicole L. Glazer, Kent D. Taylor, Tamara B. Harris, Helene Alavere, Toomas Haller, Aime Keis, Mari Liis Tammesoo, Yurii Aulchenko, In S. Barroso, Kay Tee Khaw, Pilar Galan, Serge Hercberg, Mark Lathrop, Susana Eyheramendy, Elin Org, Siim Sõber, Xiaowen Lu, Ilja M. Nolte, Brenda W. Penninx, Tanguy Corre, Corrado Masciullo, Cinzia Sala, Leif Groop, Benjamin F. Voight, Olle Melander, Christopher J. O'Donnell, Veikko Salomaa, Adamo Pio D'Adamo, Antonella Fabretto, Flavio Faletra, Sheila Ulivi, Fabiola Del Greco M, Maurizio Facheris, Francis S. Collins, Richard N. Bergman, John P. Beilby, Joseph Hung, A. William Musk, Massimo Mangino, So Youn Shin, Nicole Soranzo, Hugh Watkins, Anuj Goel, Anders Hamsten, Pierre Gider, Marisa Loitfelder, Marion Zeginigg, Dena Hernandez, Samer S. Najjar, Pau Navarro, Sarah H. Wild, Anna Maria Corsi, Andrew Singleton, Eco J C De Geus, Gonneke Willemsen, Alex N. Parker, Lynda M. Rose, Brendan Buckley, David Stott, Marco Orru, Manuela Uda, Melanie M. Van Der Klauw, Weihua Zhang, Xinzhong Li, James Scott, Yii Der Ida Chen, Gregory L. Burke, Mika Kähönen, Jorma Viikari, Angela Döring, Thomas Meitinger, Gail Davies, John M. Starr, Valur Emilsson, Andrew Plump, Jan H. Lindeman, Peter A C T Hoen, Inke R. König, Janine F. Felix, Robert Clarke, Jemma C. Hopewell, Halit Ongen, Monique Breteler, Stéphanie Debette, Anita L. Destefano, Myriam Fornage, Gary F. Mitchell, Nicholas L. Smith, Hilma Holm, Kari Stefansson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Nilesh J. Samani, Michael Preuss, Igor Rudan, Caroline Hayward, Ian J. Deary, H. Erich Wichmann, Olli T. Raitakari, Walter Palmas, Jaspal S. Kooner, Ronald P. Stolk, J. Wouter Jukema, Alan F. Wright, Dorret I. Boomsma, Stefania Bandinelli, Ulf B. Gyllensten, James F. Wilson, Luigi Ferrucci, Reinhold Schmidt, Martin Farrall, Tim D. Spector, Lyle J. Palmer, Jaakko Tuomilehto, Arne Pfeufer, Paolo Gasparini, David Siscovick, David Altshuler, Ruth J F Loos, Daniela Toniolo, Harold Snieder, Christian Gieger, Pierre Meneton, Nicholas J. Wareham, Ben A. Oostra, Andres Metspalu, Lenore Launer, Rainer Rettig, David P. Strachan, Jacques S. Beckmann, Jacqueline C M Witteman, Jeanette Erdmann, Ko Willems Van Dijk, Eric Boerwinkle, Michael Boehnke, Paul M. Ridker, Marjo Riitta Jarvelin, Aravinda Chakravarti, Goncalo R. Abecasis, Vilmundur Gudnason, Christopher Newton-Cheh, Daniel Levy, Patricia B. Munroe, Bruce M. Psaty, Mark J. Caulfield, Dabeeru C. Rao, Martin D. Tobin, Paul Elliott, Cornelia M. Van Duijn

Research output: Contribution to journalArticlepeer-review

Abstract

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10 -8 to P = 2.3 × 10 -13) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

Original languageEnglish
Pages (from-to)1005-1012
Number of pages8
JournalNature Genetics
Volume43
Issue number10
DOIs
Publication statusPublished - Oct 2011

ASJC Scopus subject areas

  • Genetics

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